Manufacture of glutaric acid



. present also in beets.

iatented Feb. 8, 1949 2,401.96 MANUFACTURE or GLUTARIC ACID Louis A. Mikeska, Westiield, N. J., assignor to Standard Oil Development Company, a corporation of Delaware No Drawing. Application April 1, 1946, Serial No. 658,877

9 Claims.

This invention pertains to a novel method of preparing glutaric acid and substituted glutaric acids. This application is a continuation in part of my copending application, Serial No. 500,843, filed September 1, 1943, now abandoned.

Glutaric acid, COHCH:CH:CH:COOH, is a constituent of the grease of sheep wool and is Several methods of synthesizing this acid have been suggested, for example, the Knoevenagel method using diethylmalonate and Formalin; by the oxidation of cyclopentanone; and by the oxidation of 1.5- pentanediol with 2% alkaline potassium permanganate solution at room temperature. In spite of these methods of synthesizing glutaric acid, its not obtainable on" the market today except as a rare chemical at high cost. 7

It is the object of this invention to provide the art with a novel method of preparing glutaric acid and substituted glutaric acids.

It is also the object of this invention to prepare glutaric acid and substituted glutaric' acids from readily available materials and by a simple procedure that forms the desired acid in pure form and in high yields,

These and other objects will appear more clearly from the detailed description and claims which follow.

It'has now been found that glutaric acid and substituted glutarlc acids may be prepared in good yields and in pure form from the condensation products of acrylonitrile with esters corresponding to the general-.formula wherein R is selected from the group consisting oi alkyl-C- and -O 0 OR R stands for hydrogen or an aliphatic group and It stands for an alkyl group.

The reactions involved in this condensation proceed with the formation of both monoand polymolecular addition products of the acrylonitrile, as follows:

acid proceeds with the rupture of the R-C bond and hydrolysis of the ester as follows? m-bnooon wherein R, R and Ti. have the meaning given a above.

' acids.

The entire preparation is quite simple. The ester is treated with about one-quarter of one percent of an alkaline condensing agent such as metallic sodium or potassium, an amine or an onium base whereupon the acrylonitrile is added with suflicient cooling to keep the temperature below C. The reaction is over in less than an hour, whereupon the excess acrylonitrile and unreacted ester is then flashed ofl and the residue is distilled under reduced pressure. If desired, the reaction mixture may be neutralized previous to distillation, with enough acetic acid to react with the alkaline condensing agent. The mononitrile is obtained in 80-90% yield based on the acrylonitrile converted and the dinitriie is obtained in 10-20% yield. The yield of the dinitrile could be increased by increasing the ratio of acrylonitrile to the ester in the original reaction.

The condensation product is converted to a glutaric acid by heating it with a strong aqueous hydrolyzing agent such as a strong aqueous acid (HCl, HBr, H2804, etc.) or a strong aqueous alkali (NaOH, KOH, LiOH, etc). For example, the condensation product may be heated with an equal volume of concentrated hydrochloric acid. Pure glutaric acid may be thus obtained in better than yield from the mononitrile condensation product with diethyl malonate. If the dinitriie is similarly heated with HCl, tricarballylic acid can be obtained.

The esters which may be used in accordance with the present invention include diethyl malonate and other esters oimalonic acid, such as the methyl, propyl or butyl esters andaceto acetic acid esters, such as methyl-, ethyl-, propyior butyl aceto acetate. It substituted esters such as alpha-n-butyl-diethyl malonate, alpha-benzyl-diethyl maionate, aipha-cetyi-diethyl malonate, alpha-n-butyl-ethyl aceto acetate, alpha-benzyi-ethyl aceto acetate or aiphacetyl-ethyl aceto acetate, are used it is possible to make the corresponding substituted glutaric The alkaline condensing agents which may be used in the initial condensationwith acrylonitrile includemetallic sodium or potassium, also sodium, potassium or ammonium hydroxides, amines, preferably tertiary amines such as tertiary ethylamine, tertiary butyl amine, dlmethyl aniline, diethyl aniline and onium bases such as cetyl trimethyl ammonium, sulfonium or phoshonium hydroxides.

funnel, drop by drop, with rapid stirring and just' enough cooling to keep the reaction temperature below 85 C. when all the acrylonitrile had been added, the reaction mixture was heated with stirring. at 85 C. for another hour.

The mixture was then cooled. Enough glacial acetic acid was added to neutralize the sodium. The reaction mixture was then distilled under 3 m. m. pressure.

gms. oi unchanged acrylonitrile and 53 gms. of dieth l malonate were recovered.

, The, reaction product yielded 187 ms. of the mononitrile boiling at 127-i30 C. and gms. of the dinitrile boiling at 1601'l0 C. The dinitrile solidified on standing. After one recrystallization from acetone it melted at 61 C.

The mononitrile was mixed with an equal weight of concentrated aqueous hydrochloric ride. On removal of the ether from the filtrate.

the residue was distilled under 3 m. m. pressure. The entire product boiled at 166 (3'. Total yield=4 gms., which corresponds to 80% of the theoretical yield of glutaric acid. This distillate consisted of a snow white solid which melted at In lieu of hydrolyzing and cracking the nitrile under acid conditions,as shown above, an alkaline treatment may also be applied, as shown by the following data:

Example II:-

A round bottom flask equipped with a return condenser was charged with 107 gms. of cyanoethyl-diethyl malonate and 500 cc. of water containing 60 gms. of sodium hydroxide. The mixture was heated on the steam bath over night.

The product was transferred into a distilling flask and most of the water was removed. The

4 tracts were combined and evaporated to dryness. The residue consisted of a 58 gms. white crystalline material, which corresponds to 90% of the theoretical yield of glutaric acid. 0n recrystallization from a mixture of ether and petroleum ether, the product melted at 97.5 C.

Instead of the ether extraction the glutaric acid may be separated from the sodium chloride and other by-products by distillation under reduced pressure.

Example IIL-Cyanoethyl-n-amvlacetoaeetate 05E omo o-d-oooolm HaOHaON A 3-way flask equipped with a mechanical stirrer, a return condenser and a thermometer w charged with gms. of n-amyl-ethylacetoacetate and 3 cc. of 40% aqueous solution of benzyl-trimethyl ammonium hydroxide. The dropping funnel was charged with 24 ms. of acrylonitrile. The latter was then added to the reactor drop by drop with rapid stirring and'just enough cooling to keep the reaction temperature below 60 C. The mixture was thenheated at C. for .3 hours with rapid stirring. When the reaction was completed, the product was cooled and poured into ice water. The cyano derivative was extracted with ether, washed free of the catalyst, and finally dried over sodium sulfate. After removal of the ether, the product was distilled under 1 m. m. pressure. Two fractions were obtained, one (34 grams) distilling at 85-155 C.. while the other (45 grams) distilled at 155-165 C. The second fraction analyzed as follows:

F H 2 I.

Hr-CHs-COOH The above described cyanoethyl acetoacetate was converted into n-amyl glutaric acid as folows:

A round bottom flask ,was charged with 30 gms. potassium hydroxide and 70 cc. of absolute alcohol. To this was then added 45 gms. of the above described cyanoethyl-n-amyl-acetcacetate. The mixture was refluxed for 4 hours whereupon it was transferred into a porcelain dish and evaporated to dryness on the steam bath. The residue consisted of a white solid material readily soluble in water. The salt was dissolved in water and acidified with concentrated hydrochloric acid. The n-amyl glutaric acid separated as an oil. This acid was extracted several times with ether. All the ether extracts were combined, washed twice with a little water and dried over sodium sulfate. on removal of the ether, the residue weighed 35 gms. and consisted of a dark red oil. The latter was distilled under 3 m. m. pressure. The major portion of the product (25 gms.) distilled at 193-19'l C. The distillate consisted of pure n-amyl glutaric acid as may be seen from the following analysis:

residue was acidified with cc. of concentrated 9 Example 1 t alpha-c gmthvl.alpha.

hydrochloric acid. The product was then evaporated to dryness under reduced pressure.

The residue which consisted of a mixture of Slutaric acid and sodium chloride was extracted several times with ethyl ether. The ether ex- A 3-way flask equipped with a mechanical stirrer, a return condenser, a thermometer and a dropping funnel, was charged with 100 ms. of alpha-n-butyl ethyl malonate. To this was then added about gram metallic sodium.

The dropping funnel was charged with 'acrylonitrile. When all the sodium had dissolved, the nitrile was added to the reactor drop by drop with rapid stirring and just enough cooling to keep the reaction temperature below C. When all the acrylonitrile had been added, the mixture was heated to C. and kept at that temperature for 1 hour.

The reaction mixture was then cooled, poured into water and acidified. The reaction product was then extracted with ether, washed, and dried over sodium sulfate. On removal oi the ether,

68 gms. of an oily residue was obtained which] was distilled under 3 m. in. pressure. The entire product distilled at -14'7 C. It analyzed as follows:

CuHggON Cale. C 62.45 H 8.55 N 5.20%

N -butyl glutartc acid canon-c 0 on m-c mo 0 on A round bottom flask was charged with 28 gms. of diethyl alpha-cyanoethyl-alpha-n-butyl malonate (described above) and 16 grams of potassium hydroxide dissolved in 200 cc. of 50% ethyl alcohol. The mixture was refluxed for 12 hrs., whereupon it was evaporated to dryness on the steam bath. The residue was then acidified with hydrochloric acid and evaporated to dryness, The semicrystalline product thus obtained was then distilled under 3 m. m. pressure. 17 gms. of a material boiling between -180 C. were obtained. The product consisted of a very viscous colorless oil which proved to be practically pure n-butyl glutaric acid as may be seen from the acid value given below: 1

0.3116. gm. of the product consumed 30.8 cc. of 0.1018 N NaOH. Hence, the acid was 94.7% pure.

The foregoing description and examples are intended to be only illustrative of the present invention. It will be obvious to those skilled in the art that numerous variations are possible without departing from the purview of this invention as defined in the following claims,

What I claim and desire to secure by Letters Patent is:

1. The process of preparing a glutaric acid which comprises subjecting a mononitrile condensation product, having the formula the group consisting of Alkyl-O-Qcnd coon- R is one of the group consisting of hydrogen and an aliphatic group and R is an alkyl group, to

heat in the presence of a hydrolyzing agent, thereby hydrolyzing the nitrile radical and split- 5 ting oil the carbonyl radical and forming a glutaric acid.

2. Process according to claim 1, in which the said hydrolyzing agent is an aqueous acid.

3. Process according to claim 1, in which the said hydrolyzing agent is aqueous hydrochloric acid.

4. Process according to claim 1, in which the hydrolyzing agent is an aqueous alkali.

5. Process according to claim 1, inwhich the hydrolyzing agent is aqueous sodium hydroxide. 6. The process of preparing a glutaric acid which comprises subjecting the mononitrile condensation product of a malonic acid ester with acrylonitrile to heat in the presence of a hydrolyzing agent, thereby hydrolyzing the nitrile radical and splitting off one carboxyl radical and forming a glutaric acid. I

, 7. The process of preparing glutaric acid which comprises subjecting the mononitrile condensation product of diethyl malonate with acrylonitrlle to heat in the presence of ahydrolyzing agent, thereby hydrolyzing the nitrile radical and splitting 011 one carboxyl radical and forming Slutarlc acid,

30 8. The process of preparing a glutaric acid which comprises subjecting the mononitrile condensation product of an aceto acetic acid ester with acrylonitrile to heat in the presence of a hydrolyzing agent, thereby hydrolyzing the nitrile radical and splitting ofl. one carbonyl radical and forming a glutaric acid.

9. The process of preparing glutaric acid which comprises subjecting the mononitrile condensation product oi ethyl aceto acetic acid with acrylonitrile to heat in the presence 01' a hydrolyzing agent, thereby hydrolyzing the nitrlle radical and splitting oil the 'acetyl, radical and forming glutaric acid.

LOUIS A. MIKESKA.

REFERENCES CITED The following references are of record in th file of this patent:

OTHER Karrer: Organic Chemistry (Eng. trans. by Mee), 1938, Nordemann Pub, 00., New York, pp, 168, 188, 251.

June 15, 1 048.

Ser. No. 874.864, Wiest (A. P. (2.). Published 

